The overall goals of this research program are to define the cellular mechanisms which control immunoglobulin production in human lymphoblasts with three specific objectives: First, to attempt to isolate spontaneous or chemically induced drug resistant (enzyme deficient) human lymphoblast mutants for use in somatic cell hybridization studies and to optimize the experimental conditions for mutagenesis of diploid human lymphoblasts; Second, to hybridize immunoglobulin producing lymphoblasts with other mammalian cells both producing and not producing immunoglobulins to study the mechanisms restricting antibody production in human leukocytes, and third, to study the phenotypic stability of human lymphoblast cells to determine the spontaneous and induced frequency of loss of immunoglobulin gene expression and whether this is related to chromosomal abnormalities appearing in cultured cells possibly useful for determining the chromosomal location of immunoglobulin genes.